The plant kava-kava (piper methysticum Forst. Piperaceae) is native to Polynesia. An intoxicating beverage made from its crushed roots has been used in ceremonies since ancient times.
Kava-kava has been found to have significant analgesic and anesthetic effects via non-opiate pathways. It also can be used as phytotranquilizer to reduce nervousness and overexcitement. However, kava-kava""s most popular application is as a natural anxiolytic and has compared favorably to a number prescription medications such as benzodiazepines. Kava-kava""s pharmacological activity has been attributed to lactones present in the plant roots.
Several kava-kava products are available, such as kava-kava-based beverages, kava-kava ethanol extract solutions, kava-kava emulsions with glycerin and coconuts oil dispersed in water, and kava-kava extract tablets. Unfortunately, the active lactones in kava-kava-based products have low bioavailability since the lactones themselves are practically insoluble in water. For example, the maximum solubility of kawain at 21xc2x0 C. is about 2.2 mg/100 ml water. Accordingly, high doses of kava-kava-based products or the active lactones are required to obtain therapeutic effects.
In one aspect, the invention features a method of obtaining a kava-kava lactone-containing product by heating pulverized kava roots in an aqueous solution which contains a cyclodextrin-based solubilizing agent to extract kava-kava lactones from the pulverized kava-kava roots.
In another aspect, the kava-kava lactone-containing product in dried form includes greater than about 50 parts by weight (e.g., about 50 to about 99 parts by weight) of one or more of the active kava-kava lactones and has a solubility of at least about 0.05 mg/ml (e.g., about 0.05 mg/ml to about 25 mg/ml), preferably greater than about 0.1 mg/ml, and most preferably greater than about 1 mg/ml in water at about 25xc2x0 C.
The cyclodextrin-based solubilizing agent includes xcex1, xcex2, or xcex3 forms of cyclodextrin and derivatives thereof. xcex1-cyclodextrin is a ring of six glucose residues, xcex2-cyclodextrin is a ring of seven glucose residues, and xcex3-cyclodextrin is a ring of eight glucose units. Examples of cyclodextrin-based solubilizing agents, include but are not limited to, xcex1, xcex2, or xcex3 forms of cyclodextrin, hydroxypropylcyclodextrin, hydroxyethylcyclodextrin, glucosylcyclodextrin, maltosylcyclodextrin, and maltotriosylcyclodextrin. See, for example, U.S. Pat. No. 5,997,856.
In another aspect, the invention features a method of removing flavokawains from a crude kava-kava lactone-containing preparation. The method includes heating the crude kava-kava lactone-containing preparation in an aqueous solution which contains a cyclodextrin-based solubilizing agent to solubilize kava-kava lactones and thereby produce an aqueous kava-kava lactone-containing solution; and removing flavokawains from the solution, such as by filtering. Crude kava-kava lactone-containing preparations, typically, are produced by extracting pulverized kava-kava root with an organic solvent and are commercially available as kava-kava extracts.
In yet another aspect, the invention features a solubilized kava-kava root extract in aqueous form including active kava-kava lactones in a concentration greater than 0.05, preferably greater than about 0.1, and most preferably greater than about 1 weight percent of the extract, and flavokawains in a concentration of less than about 0.3 weight percent of the extract.
In still another aspect, the invention features a solubilized kava-kava root extract in dried form including active kava-kava lactones in a concentration greater than about 50 weight percent of the extract, and flavokawains in a concentration of less than about 0.3 weight percent of extract.
The kava-kava lactone-containing product (i.e., kava-kava root extract) of this invention exhibits desirable composition and performance. It has a high content of kava-kava lactones and a low content of flavokawains, and increased bioavailability and skin permeability of kava-kava lactones when used as an ingredient in a food, pharmaceutical, or cosmetic product.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.